Prognostic value of serum androgens, by ultrasensitive assay, in metastatic castration-resistant prostate cancer (mCRPC): Phase III trial data.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 22-22
Author(s):  
Charles J. Ryan ◽  
Arturo Molina ◽  
Jinhui Li ◽  
Thian San Kheoh ◽  
Eric Jay Small ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Positive Association ◽  
Serum Testosterone ◽  
Serum Levels ◽  
Dehydroepiandrosterone Sulfate ◽  
Cox Proportional Hazards ◽  
Mass Spectrometric ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Baseline Serum

22 Background: Serum testosterone (T) and precursors, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (A4), may be prognostic of overall survival (OS) by identifying patients (pts) with varying dependency on androgen. To test this hypothesis, we investigated the relationship between the distribution of serum androgen concentrations measured by ultrasensitive mass spectrometric assays with OS, in pts with mCRPC treated in COU-AA-301, a randomized phase III study of abiraterone acetate (AA)(1000mg) plus prednisone (P) vs P. Methods: Pts were stratified by ECOG PS (0-1 vs 2), pain (present vs absent), prior chemotherapy regimens (1 vs 2), and type of progression (PSA only vs radiographic). Eligibility required baseline T ≤50 ng/dL. In a post hoc exploratory analysis, the effect of baseline serum androgen levels (T, DHEAS, A4) on OS (95% CI, months), stratified by quartiles of each androgen was determined. T, DHEAS, and A4 serum levels were measured using novel liquid-liquid extraction 1D or 2D-LC/tandem mass spectrometry ((LC)-LC-MS/MS) assays. Univariate and multivariate analyses using the Cox proportional hazards regression model were performed. Results: Baseline T levels were available from 97% of pts (93% with baseline T ≤15 ng/dL). Median OS increased in a step-wise fashion per T quartile, regardless of treatment (p<0.0001) (Table). Similar results were observed for DHEAS and A4. A positive association was observed in the multivariate analysis adjusted for treatment, other androgens, and lab parameters (LDH, HGB, ALKP, PSA; all p<0.0001). In AA and P-treated pts, respectively, the hazard ratio for OS (95% CI) comparing pts with baseline T above and below baseline median was 0.64 (0.53-0.77; p<0.0001) and 0.51 (0.39-0.67; p=0.0004). Conclusions: Baseline serum androgen concentrations as measured by an ultrasensitive mass spectrometric assay may be prognostic of OS in mCRPC pts and bear consideration as a stratification variable in phase III studies. Clinical trial information: NCT00638690. [Table: see text]

Overall survival (OS) and metastasis-free survival (MFS) by depth of prostate-specific antigen (PSA) decline in the phase III PROSPER trial of men with nonmetastatic castration-resistant prostate cancer (nmCRPC) treated with enzalutamide (ENZA).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 94-94
Author(s):  
Maha H. A. Hussain ◽  
Cora N. Sternberg ◽  
Eleni Efstathiou ◽  
Karim Fizazi ◽  
Qi Shen ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Reference Group ◽  
Specific Antigen ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Analysis Model ◽  
Increased Risk ◽  
Psa Nadir ◽  
Post Hoc

94 Background: The PROSPER trial demonstrated prolonged MFS and OS for men with nmCRPC and rapidly rising PSA treated with ENZA vs placebo, both in combination with androgen deprivation therapy (ADT). The final survival analysis of PROSPER (Sternberg et al. NEJM 2020) recently reported a median OS of 67.0 months (95% CI, 64.0 to not reached) with ENZA and 56.3 months (95% CI, 54.4 to 63.0) with placebo (hazard ratio [HR] for death, 0.73; 95% CI, 0.61 to 0.89; P = .001). Post hoc analyses of PROSPER evaluating PSA dynamics have demonstrated longer MFS with greater PSA decline (Hussain et al. ESMO Sept 19-21, 2020. Poster 685P) and increased risk of metastases in patients with even modest PSA progression vs those without (Saad et al. Eur Urol 2020). Here we further explored the relationship between PSA dynamics and outcomes in PROSPER using uniquely defined PSA subgroups of decline. Methods: Eligible men in PROSPER had nmCRPC, a PSA level ≥ 2 ng/mL at baseline, and a PSA doubling time ≤ 10 months. Men continued ADT, were randomized 2:1 to ENZA 160 mg once daily vs placebo, and had PSA evaluation at week 17 and every 16 weeks thereafter. This post hoc analysis evaluated OS and MFS for 4 mutually exclusive subgroups defined by PSA nadir using men with PSA reduction < 50% as the reference group. The HR is based on an unstratified Cox proportional hazards analysis model. Results: 1401 men were enrolled in PROSPER; 933 were treated with ENZA and PSA data were available for 905. Measured at nadir, 38% of these men achieved PSA reduction ≥ 90% (actual nadir < 0.2 ng/mL), and another 27% achieved PSA reduction ≥ 90% (actual nadir ≥ 0.2 ng/mL). Among men in the placebo arm of PROSPER only 3/457 reported PSA reduction ≥ 90%. Median OS and MFS increased with increasing depth of PSA decline (Table). Conclusions: In men with nmCRPC and rapidly rising PSA treated with ADT plus ENZA, there was a close relationship between the degree of PSA decline and survival outcomes. Defining PSA by both percent decline and actual decline below 0.2 ng/mL revealed a previously under-appreciated relationship between these PSA metrics and highlights the importance of PSA nadir as an intermediate biomarker in nmCRPC. Clinical trial information: NCT02003924. [Table: see text]

Association between radiographic response and overall survival in men with metastatic castration-resistant prostate cancer receiving chemotherapy.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 118-118
Author(s):  
G. Sonpavde ◽  
G. R. Pond ◽  
W. R. Berry ◽  
R. De Wit ◽  
M. A. Eisenberger ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Objective Assessment ◽  
Objective Response ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Kaplan Meier

118 Background: In men with metastatic castration resistant prostate cancer (CRPC),the association of measurable tumor responses with overall survival (OS) is unknown. We retrospectively evaluated the TAX327 phase III trial to study this relationship. Methods: Eligible patients for this analysis included those with WHO-defined measurable metastatic disease randomized to receive either docetaxel or mitoxantrone. OS was estimated using the Kaplan-Meier method and the prognostic relationship of WHO-defined radiologic response with OS was performed using Cox proportional hazards regression. Landmark analyses evaluated survival from baseline and 2, 3, 4 and 6 months after baseline. Results: Four hundred and twelve patients enrolled on the TAX327 trial had measurable tumors. Thirty-seven patients exhibited a complete or partial objective response (CR/PR, 9.0%), 116 had stable disease (SD, 28.2%), 99 had progressive disease (PD,24%) and 160 (38.8%) did not have a post-baseline objective assessment. Partial responders demonstrated longer median OS (29.0 months) than patients with SD (22.1 months), or those with PD (10.8 months) or those who were not assessed (12.7 months). These results remained after landmark analysis. We found a significant association between ≥30% PSA declines and radiologic response, with ≥30% PSA declines occurring in all patients with CR/PR, 79.8% of patients with SD and 34.4% with PD. Radiologic response remained a significant but modest post-treatment prognostic factor for OS after adjusting for treatment, pain-response and ≥30% PSA-decline (p=0.009). Conclusions: In men with metastatic CRPC and measurable disease receiving chemotherapy, objective tumor response was prognostic for OS, and appears to complement PSA assessment. [Table: see text]

scholarly journals 177 Lu-PSMA-617 radioligand therapy of metastatic castration-resistant prostate cancer: Initial 254-patient results from a prospective registry (REALITY Study)

2021 ◽  
Author(s):  
Fadi Khreish ◽  
Zaidoon Ghazal ◽  
Robert J. Marlowe ◽  
Florian Rosar ◽  
Amir Sabet ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Proportional Hazards ◽  
Specific Antigen ◽  
Cox Proportional Hazards ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Baseline Serum ◽  
Castration Resistant ◽  
Patient Reported ◽  
End Stage

Abstract Purpose Preliminary data from retrospective analyses and recent data from large randomized controlled trials suggest safety and efficacy of radioligand therapy (RLT) targeting prostate-specific membrane antigen (PSMA) in men with metastatic castration-resistant prostate cancer (mCRPC). Limited data on this modality have been published regarding large samples treated in everyday practice. Methods We analyzed prospectively collected registry data regarding lutetium-177 (177Lu)-PSMA-617 RLT of 254 consecutive men with mCRPC seen in everyday academic practice. Since 177Lu-PSMA-617 was experimental salvage treatment following failure of individually appropriate conventional therapies, patients were generally elderly and heavily pretreated (median age 70 years; prior taxanes 74.0%, 188/254), with late–end-stage disease (visceral metastasis in 32.7%, 83/254). Primary endpoints were response to RLT, defined by changes from baseline serum prostate-specific antigen (PSA) concentration, PSA progression-free survival (PSA-PFS), and overall survival (OS), estimated with Kaplan–Meier statistics, and caregiver-reported and patient-reported safety. Unless noted, median (minimum–maximum) values are given. Results Patients received 3 (1–13) 177Lu-PSMA-617 activities (6.5 [2.5–11.6] GBq/cycle) every 5.7 (3.0–11.0) weeks. Best response was ≥ 50% PSA reduction in 52.0% of patients (132/254). PSA-PFS was 5.5 (95% confidence interval [95%CI] 4.4–6.6) months and OS, 14.5 (95%CI 11.5–17.5) months. In multivariable Cox proportional-hazards modeling, response to the initial ≤ 2 RLT administrations was the strongest significant prognosticator related to OS (hazard ratio 3.7 [95%CI 2.5–5.5], p < 0.001). No RLT-related deaths or treatment discontinuations occurred; the most frequent RLT-related Grade 3/4 adverse events were anemia (18/254 patients, 7.1%), thrombocytopenia (11/254, 4.3%), and lymphopenia (7/254, 2.8%). RLT-related xerostomia, all grade 1/2, was noted in 53/254 (20.9%). Conclusions In a large, prospectively observed “real-world” cohort with late-stage/end-stage mCRPC and conventional treatment failure, 177Lu-PSMA-617 RLT was effective, safe, and well-tolerated. Early biochemical disease control by such therapy was associated with better OS. Prospective study earlier in the disease course may be warranted.

scholarly journals Association of serum 25-hydroxyvitamin D with prevalence, incidence, and clearance of vaginal HPV infection in young women

2020 ◽  
Author(s):  
Mariam El-Zein ◽  
Farzin Khosrow-Khavar ◽  
Ann N Burchell ◽  
Pierre-Paul Tellier ◽  
Shaun Eintracht ◽  
...  
Keyword(s):  
Vitamin D ◽  
Proportional Hazards ◽  
Hpv Infection ◽  
Cox Proportional Hazards ◽  
Baseline Serum ◽  
Hpv Dna ◽  
Hydroxyvitamin D ◽  
Hpv Prevalence ◽  
Vitamin D Levels ◽  
25 Hydroxyvitamin D

Abstract Background We assessed the association between serum 25-hydroxyvitamin D levels and genital human papillomavirus (HPV) prevalence, incidence, and clearance among female participants of the HITCH cohort study. Methods We genotyped HPV DNA in vaginal samples and quantified baseline serum 25-hydroxyvitamin D levels using Roche’s Linear Array and Total vitamin D assay, respectively. We used logistic and Cox proportional hazards models to respectively estimate adjusted odds ratios (OR) and hazards ratios (HR) with 95% confidence intervals (CI). Results There was no association between vitamin D levels (every 10ng/mL increase) at baseline and HPV prevalence (OR=0.88, CI:0.73-1.03) or incidence (HR=0.88, CI:0.73-1.06), but we observed a modest negative association with HPV clearance (HR=0.76, CI:0.60-0.96). Vitamin D levels &lt;30ng/mL, compared to ≥30ng/mL, were not associated with HPV prevalence (OR=0.98, CI:0.57-1.69) or incidence (HR=0.87, CI:0.50-1.43), but were associated with a marginally significant increased clearance (OR=2.14, CI:0.99-4.64). We observed consistent results with restricted cubic spline modelling of vitamin D levels and clinically defined categories. HPV type-specific analyses accounting for multiple HPV infections per participant showed no association between vitamin D levels and all study outcomes. Conclusion This study provided no evidence of an association between low vitamin D levels and increased HPV prevalence, acquisition, or clearance.

Abstract MP012: Plasma Galectin-3 Levels and Subsequent Risk of Incident Chronic Kidney Disease

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Casey M Rebholz ◽  
Elizabeth Selvin ◽  
Menglu Liang ◽  
Christie M Ballantyne ◽  
Ron C Hoogeveen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Proportional Hazards ◽  
Disease Risk ◽  
Positive Association ◽  
Cox Proportional Hazards ◽  
Diabetes Status ◽  
Incident Chronic Kidney Disease ◽  
Galectin 3

Introduction: Galectin-3 is a 35 kDa β-galactoside-binding lectin which has been proposed as a novel biomarker of heart failure primarily due to its involvement in myocardial fibrosis. Elevated levels of galectin-3 may be associated with fibrosis of other organs, such as the kidney, and increase the risk of developing kidney disease. Methods: Using Cox proportional hazards regression, we prospectively analyzed Atherosclerosis Risk in Communities (ARIC) study participants with measurements of plasma galectin-3 levels at baseline (visit 4, 1996-98) and without prevalent kidney disease or heart failure (N=9,647). Incident chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 accompanied by 25% eGFR decline, chronic kidney disease-related hospitalization or death, or end-stage renal disease between baseline and December 31, 2013. Results: 2,105 participants (22%) developed incident chronic kidney disease over a median follow-up of 16 years. The mean (standard deviation) plasma level of galectin-3 was 14.7 (4.4) ng/mL. At baseline, galectin-3 was cross-sectionally associated with eGFR (r = -0.31) and urine albumin-to-creatinine ratio (UACR) (r = 0.19). After adjusting for demographics and kidney disease risk factors, there was a significant, graded, and positive association between galectin-3 and incident chronic kidney disease (quartile 4 vs. 1 HR: 1.84, 95% CI: 1.62, 2.09, p for trend <0.001). The association between galectin-3 and incident chronic kidney disease was attenuated but remained significant after accounting for eGFR and UACR (quartile 4 vs. 1 HR: 1.58, 95% CI: 1.39, 1.80, p for trend <0.001). The association was similar by diabetes status (p for interaction = 0.33) and stronger among those with hypertension (p for interaction = 0.004). Conclusion: In this community-based population, higher plasma galectin-3 levels were associated with elevated risk of developing incident chronic kidney disease, particularly among those with hypertension.

scholarly journals Effect of Blood Pressure on Cardiovascular Outcomes: A 15-Year Prospective Cohort Study

2021 ◽  
Author(s):  
Qi Yu ◽  
Qing-Dong Jin
Keyword(s):  
Blood Pressure ◽  
Proportional Hazards ◽  
Positive Association ◽  
Cubic Spline ◽  
Cox Proportional Hazards ◽  
Cardiovascular Outcomes ◽  
Composite Outcome ◽  
Nutrition Survey ◽  
Cox Models ◽  
Diabetes Status

Abstract Objective The association between blood pressure(BP) and cardiovascular outcomes has not been well investigated by large prospective studies on Chinese. We aim to analyze the association of BP with cardiovascular outcomes in Chinese population. Method We included a total of 4,569 adults aged 40–90 years from the China Health and Nutrition Survey (CHNS) cohort. Cox proportional hazards regression models were used to estimate hazard ratios and 95% CIs. Restricted cubic spline analyses were used to explore linear and nonlinear relationships of BP with cardiovascular outcomes. Result With a mean follow-up of 12.1 years, a total of 4,569 individuals were enrolled in our study, of whom 403 developed cardiovascular outcomes. Multivariable adjusted Cox models showed a strong positive association between BP and cardiovascular outcomes. SBP was significantly associated with composite outcome(HR per 10 mmHg 1.23[1.16–1.29]), myocardial infarction(MI)(HR per 10 mmHg 1.17[1.07–1.27]), and stroke(HR per 10 mmHg 1.29[1.21–1.38]). DBP was significantly associated with composite outcome(HR per 10 mmHg 1.32[1.20–1.44]), MI(HR per 10 mmHg 1.26[1.10–1.44]), and stroke(HR per 10 mmHg 1.39[1.25–1.55]). Restricted cubic spline analyses showed linear relationships of either SBP or DBP with composite outcome, MI and stroke. Conclusion Either SBP or DBP is independently and linearly related to the risk of cardiovascular outcomes. These associations are steeper for stroke than for MI, and vary widely by age, use of antihypertensive treatment, and diabetes status.

Serum cholinesterase levels to predict all-cause mortality in a community-based study: The Takahata study

2021 ◽  
Author(s):  
Makoto Saegusa ◽  
Yumi Matsuda ◽  
Tsuneo Konta ◽  
Takafumi Saitoh ◽  
Kaori Sakurada ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Independent Predictor ◽  
Correlation Coefficients ◽  
Cox Proportional Hazards ◽  
Serum Cholinesterase ◽  
Community Based ◽  
Baseline Serum ◽  
Middle Group ◽  
Kaplan Meier ◽  
All Cause Mortality

Introduction: Serum albumin (Alb) levels have been found to be independent predictors of all-cause mortality in a community-based population, but whether this is the case for serum cholinesterase (ChE) levels is uncertain. This study aimed to determine whether serum ChE levels are independent predictors of all-cause mortality in a community-based population. Methods: A total of 3,504 subjects (mean age 62.5 years) from Takahata, Japan participated and were followed up for 13.5 years (median 13.2 years). Based on baseline serum Alb and ChE levels, subjects were stratified by interquartile range as low, middle, and high. The correlation between serum Alb and ChE levels was examined by calculating correlation coefficients. The association between each group and all-cause mortality was examined by Kaplan-Meier and Cox proportional hazards analysis. Results: During follow-up, 568 subjects died. There was a positive correlation between serum Alb and ChE levels (r=0.30). Kaplan-Meier analysis showed that all-cause mortality in the low group was significantly higher for both serum Alb and ChE levels (log-rank P<0.01). Adjusted Cox proportional hazards analysis showed that the serum Alb level was not an independent predictor of all-cause mortality (hazard ratio (HR) 1.18, 95% confidence interval (CI) 0.95-1.46 for all-cause mortality in the low group compared to the middle group), whereas the serum ChE level was an independent predictor of all-cause mortality (HR 1.30, 95% CI 1.06-1.59 for all-cause mortality in the low group compared to the middle group). Conclusion: The serum ChE level is an independent predictor of all-cause mortality in the general community-based population.

Body weight loss (BWL) as a prognostic/predictive factor in previously treated patients (pts) with metastatic gastric or gastroesophageal junction cancer (mGC/GEJC): Post-hoc analyses of the phase III tags trial.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 476-476
Author(s):  
Michele Ghidini ◽  
Howard S. Hochster ◽  
Toshihiko Doi ◽  
Eric Van Cutsem ◽  
Lukas Makris ◽  
...  
Keyword(s):  
Body Weight ◽  
Prognostic Factors ◽  
Proportional Hazards ◽  
Cox Model ◽  
Gastroesophageal Junction ◽  
Body Weight Loss ◽  
Cox Proportional Hazards ◽  
Phase Iii ◽  
Body Weight Data ◽  
Grade 3

476 Background: Nutritional status is closely linked to cancer mortality, and BWL has been shown to be prognostic for survival in curative, first-, and second-line settings in mGC/GEJC. In the phase III TAGS trial, trifluridine/tipiracil (FTD/TPI) showed clinical benefit versus placebo (PBO) and manageable safety in pts with mGC/GEJC who had received ≥2 prior chemotherapy regimens. The association of early BWL with survival outcomes in TAGS was examined in retrospective analyses. Methods: The TAGS intent-to-treat (ITT) population was categorized into pts who experienced <3% or ≥3% BWL from the start of treatment until day 1 of cycle 2 (each cycle: 28 days). Overall survival (OS), and progression-free survival (PFS) were compared between subgroups within each treatment arm due to significant imbalances of early BWL between treatment arms. The effect of early BWL on OS was assessed by a univariate Cox proportional hazards (PH) model as well as a multivariate Cox PH model that adjusted for baseline prognostic factors identified in the original ITT analysis. Results: Body weight data were available for 451 of 507 (89%) pts in the study (n=304, FTD/TPI; n=147, PBO). In the FTD/TPI and PBO arms, respectively, 74% (224/304 pts) and 65% (95/147) experienced <3% BWL, whereas 26% (80/304) and 35% (52/147) experienced ≥3% BWL at the end of cycle 1. Pts with <3% BWL had longer OS than those with ≥3% BWL in both FTD/TPI (median [m] OS: 6.5 vs 4.9 months [mo]; hazard ratio [HR], 0.75; 95% CI, 0.55–1.02) and PBO arms (mOS: 6.0 vs 2.5 mo; HR, 0.32; 95% CI, 0.21–0.49). The PFS HR for pts with <3% BWL vs ≥3% BWL was 0.95 (95% CI, 0.71–1.25; mPFS, 2.1 vs 1.9 mo) in the FTD/TPI group and 0.49 (95% CI, 0.34–0.72; mPFS, 1.9 vs 1.7 mo) in the PBO group. In the pooled ITT population, the unadjusted HR for the <3% vs ≥3% BWL group calculated using a univariate Cox model was 0.58 (95% CI, 0.46–0.73), indicating a strong prognostic effect of early BWL. Results of multivariate analyses were consistent with univariate analyses and suggested that early BWL was both a prognostic ( P<0.0001) and predictive (interaction P=0.0003) factor for OS in pts with mGC/GEJC. Grade ≥3 adverse events (AEs) of any cause were reported in 77% and 82% of FTD/TPI-treated pts in the <3% and ≥3% BWL subgroups, respectively, and in 45% and 67% of placebo-treated pts in the <3% and ≥3% BWL subgroups. Conclusions: To our knowledge, this is the first analysis to show that BWL is negatively associated with survival in pts with mGC/GEJC receiving third- or later-line treatment. In TAGS, early BWL (≥3% BWL at the end of cycle 1) was a strong negative prognostic factor for OS regardless of FTD/TPI or PBO treatment. Grade ≥3 AE frequencies were similar in FTD/TPI-treated pts with <3% or ≥3% BWL. The relationship of BWL to other prognostic factors will be explored further. Clinical trial information: NCT02500043.

scholarly journals Baseline Serum Bilirubin and Risk of First Stroke in Hypertensive Patients

2020 ◽  
Vol 9 (12) ◽  
Author(s):  
Jiancheng Wang ◽  
Xianglin Zhang ◽  
Zhuxian Zhang ◽  
Yuanyuan Zhang ◽  
Jingping Zhang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Proportional Hazards ◽  
Total Bilirubin ◽  
Serum Bilirubin ◽  
Cox Proportional Hazards ◽  
Direct Bilirubin ◽  
Serum Total Bilirubin ◽  
Inverse Association ◽  
Baseline Serum ◽  
Hypertensive Patients

Background Data on the association between serum bilirubin and the risk of stroke are limited and inconclusive. We aimed to evaluate the association between serum bilirubin and the risk of first stroke and to examine any possible effect modifiers in hypertensive patients. Methods and Results Our study was a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). A total of 19 906 hypertensive patients were included in the final analysis. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for the risk of first stroke associated with serum bilirubin levels. The median follow‐up period was 4.5 years. When serum total bilirubin was assessed as tertiles, the adjusted HR of first ischemic stroke for participants in tertile 3 (12.9–34.1 μmol/L) was 0.75 (95% CI, 0.59–0.96), compared with participants in tertile 1 (<9.3 μmol/L). When direct bilirubin was assessed as tertiles, a significantly lower risk of first ischemic stroke was also found in participants in tertile 3 (2.5–24.8 μmol/L) (adjusted HR, 0.77; 95% CI, 0.60–0.98), compared with those in tertile 1 (<1.6 μmol/L). However, there was no significant association between serum total bilirubin (tertile 3 versus 1: adjusted HR, 1.45; 95% CI, 0.89–2.35) or direct bilirubin (tertile 3 versus 1: adjusted HR, 1.27; 95% CI, 0.76–2.11) and first hemorrhagic stroke. Conclusions In this sample of Chinese hypertensive patients, there was a significant inverse association between serum total bilirubin or direct bilirubin and the risk of first ischemic stroke.

scholarly journals Serum Testosterone is Inversely and Sex Hormone-binding Globulin is Directly Associated with All-cause Mortality in Men

2020 ◽  
Author(s):  
Bu B Yeap ◽  
Ross J Marriott ◽  
Leen Antonio ◽  
Yi X Chan ◽  
Suchitra Raj ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Serum Testosterone ◽  
Cox Proportional Hazards ◽  
Community Dwelling ◽  
Sex Hormone ◽  
Sex Hormone Binding Globulin ◽  
Atherosclerotic Cardiovascular Disease ◽  
Hormone Binding ◽  
Baseline Serum ◽  
Related Mortality

Abstract Context Serum testosterone concentrations decline with age, while serum sex hormone-binding globulin (SHBG) concentrations increase. Objective To analyze associations of baseline serum testosterone and SHBG concentrations, and calculated free testosterone (cFT) values, with all-cause and cause-specific mortality in men. Design, Setting, and Participants The UK Biobank prospective cohort study of community-dwelling men aged 40–69 years old, followed for 11 years. Main Outcome Measures All-cause, atherosclerotic cardiovascular disease (CVD) and cancer-related mortality. Cox proportional hazards regression was performed, adjusting for age, waist circumference, medical conditions, and other covariates. Models for testosterone included SHBG and vice versa. Results In a complete case analysis of 149 436 men with 10 053 deaths (1925 CVD and 4927 cancer-related), men with lower testosterone had a higher mortality rate from any cause (lowest vs highest quintile, Q1 vs Q5, fully-adjusted hazard ratio [HR] = 1.14, 95% confidence interval [CI] = 1.06–1.22, overall trend P &lt; 0.001), and cancer (HR = 1.20, CI = 1.09–1.33, P &lt; 0.001), with no association for CVD deaths. Similar results were seen for cFT. Men with lower SHBG had a lower mortality rate from any cause (Q1 vs Q5, HR = 0.68, CI = 0.63–0.73, P &lt; 0.001), CVD (HR = 0.70, CI = 0.59–0.83, P &lt; 0.001), and cancer (HR = 0.80, CI = 0.72–0.89, P &lt; 0.001). A multiply imputed dataset (N = 208 425, 15 914 deaths, 3128 CVD-related and 7468 cancer-related) and analysis excluding deaths within the first 2 years (9261, 1734, and 4534 events) yielded similar results. Conclusions Lower serum testosterone is independently associated with higher all-cause and cancer-related, but not CVD-related, mortality in middle-aged to older men. Lower SHBG is independently associated with lower all-cause, CVD-related, and cancer-related mortality. Confirmation and determination of causality requires mechanistic studies and prospective trials.

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